Interestingly, EGFR inhibition with afatinib led to increased levels of p-STAT3 Y705 in both BT50 (EGFR wt) and BT73 (EGFRvIII mt) (Figure 1D and Supplementary Figure S1E), but not in p-AKT or p-MAPK (through a TNF activation response), which have also been previously described as possible mechanisms of resistance following EGFR inhibition in lung cancer30 and glioma,31 respectively (Figure 1D). Here, STAT3 is linked to glioma.